Differential modulation of nociceptive dural input to [hypocretin] orexin A and B receptor activation in the posterior hypothalamic area

Pain. 2004 Jun;109(3):367-378. doi: 10.1016/j.pain.2004.02.005.


The novel neuropeptides orexin A and B are selectively synthesised in the lateral and posterior hypothalamus and are involved in hypothalamic regulation of autonomic and neuroendocrine functions. Recent findings point also to a role in nociception. As the posterior hypothalamus is involved in the central modulation of nociception we studied the effects of hypocretin/orexin receptor activation in the posterior hypothalamic area (PH) of the rat on dural nociceptive input. Orexins were microinjected into the PH and the effects on responses of neurones in the caudal trigeminal nucleus studied. Injection of orexin A decreased the A- and C-fibre responses to dural electrical stimulation as well as spontaneous activity. Responses to noxious thermal stimulation of the facial skin were also decreased by orexin A. Injection of orexin B into the PH, however, elicited increased responses to dural stimulation in A- and C-fibre responses and resulted in increased spontaneous activity. Responses to facial thermal stimulation were also increased by orexin B. Control injection of saline into the PH had no significant effect. The results show a differential modulation of dural nociceptive input by orexin A and B receptor activation in the PH. The results support the role of the PH in the nociceptive processing of meningeal input. As both peptides are also involved in hypothalamic regulation of neuroendocrine and autonomic functions, orexinergic mechanisms in the PH may provide a link for endocrine and autonomic changes as well as nociceptive phenomena seen in primary headache disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Carrier Proteins / metabolism
  • Carrier Proteins / pharmacology
  • Dura Mater / physiopathology*
  • GABA Antagonists / pharmacology
  • Headache / physiopathology
  • Hypothalamus, Posterior / cytology
  • Hypothalamus, Posterior / drug effects
  • Hypothalamus, Posterior / metabolism*
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / physiology
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neurons / drug effects
  • Neurons / physiology
  • Neuropeptides / metabolism
  • Neuropeptides / pharmacology
  • Nociceptors / physiology*
  • Orexin Receptors
  • Orexins
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide / agonists
  • Receptors, Neuropeptide / metabolism*
  • Trigeminal Caudal Nucleus / cytology
  • Trigeminal Caudal Nucleus / physiology
  • Trigeminal Nerve / physiology*


  • Carrier Proteins
  • GABA Antagonists
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide